Cancer is the leading cause of mortality in the United States, despite many advances in the current therapies including surgery, radiation and chemotherapy. Therefore, it is imperative that novel targets for cancer therapeutic development are identified and explored in order to improve the outcome of this lethal disease. We recently exclusively licensed a novel gene named EG-1 (endothelial derived gene-1). EG-1 expression is elevated in several cancer epithelial cell types, including human breast, colorectal and prostate cancer. Transfection studies showed that over- expression of EG-1 increases cellular proliferation in vitro and xenograft tumor growth in vivo. EG-1 inhibition, whether delivered via siRNA lentivirus or polyclonal antibody, results in decreased breast cancer cellular proliferation in culture and smaller xenografts in mice. In a series of invasive breast cancer, EG-1 is an independent and significant predictor for survival. Based on this preliminary data, we hypothesize that EG-1 plays a crucial role in stimulating malignant epithelial cell proliferation. In this research proposal, we will validate the functional significance of EG-1 in breast cancer growth. The specific aim is to suppress breast tumor growth with EG-1 targeted strategies. We will produce and assess the impact of anti-EG-1 antibodies for their ability to suppress breast cancer growth. The data obtained from this grant proposal will form the basis for the successful translation of the discovery of this molecule into possible human use. PUBLIC HEALTH RELEVANCE: Cancer is the most deadly disease in the United States, and there is an urgent need of new and effective treatments for this lethal condition. This project is highly innovative because: 1) EG-1 is a completely novel gene licensed by our company. It has no significant homology to any known or established gene families. 2) If successful, this research can result in a brand new treatment for epithelial-derived cancer, which is the most common type of malignancy. 3) Because EG-1 is unique, its use as a therapeutic target would not be redundant to other gene products/potential targets involved in other molecular pathways.